D Messerer’s research while affiliated with University of Rostock and other places

Due to eligibility criteria not all patients with the disease under investigation can be recruited for therapeutic studies. Thus, the external validity of study results cannot per se be taken for granted. The representativity of the admitted patients is the most relevant determinant for external validity and has to be assessed. As an example we examined the representativity of the patients recruited for the German multicenter study group for adult acute lymphoblastic leukemia (ALL) (GMALL). Lacking nationwide ALL incidence figures available in Germany, a methodology was developed to estimate incidence figures, too. All relevant study groups, hospitals, and diagnostic labs were asked to provide data about patients with ALL newly diagnosed between 1997 and 1998. A matching procedure was developed, as heterogeneous databases had to be pooled and checked for duplicates. Age- and sex-specific incidences of ALL were estimated and compared with the number of patients recruited for the GMALL in the same time period. The purpose was to develop a methodology for estimating incidence figures and evaluating the representativity of patients of the GMALL. The combination of various data sources allowed estimation of reliable incidence data for ALL in Germany. Comparisons with the incidence figures for ALL in other countries and crosschecks within Germany confirm our results. Sixty-two percent of all ALL patients in Germany were admitted to the GMALL study. The recruitment rate of more than 60% of the annual incidence of ALL to the GMALL suggests a high external validity as well as an impact of the study on the patterns of treatment and referral of ALL in adults in Germany. There is no selection bias of patients admitted to the GMALL compared to those patients not included in the study.

It is usually not possible to generalise conclusions from a therapeutic study to the whole population because of the select nature of the study population. The situation seems to be, however, different in the German Multicentre Study Group For Adult ALL on acute lymphoblastic leukaemia GMALL (Gökbuget et al. 2000), age 15-64, because more than a hundred centres are recruiting in Germany.

Die akute lymphatische Leukämie macht etwa 20% der akuten Leukämien des Erwachsenenalters aus. Die Gesamtinzidenz liegt bei 3–4 Fällen/100.000 pro Jahr wobei der Häufigkeitsgipfel im Alter unter 10 Jahren liegt. Die Symptome der ALL sind eher unspezifisch und resultieren meist aus der Durchsetzung des Knochenmarks mit unreifen lymphatischen Blasten und der entsprechenden Suppression der normalen Hämatopoese. Alle anderen Organe können jedoch ebenfalls einen leukämischen Befall aufweisen. Obwohl in den meisten Fällen lymphatische Blasten im Differenzialblutbild erkennbar sind, ist eine Knochenmarkpunktion mit entsprechenden Spezialuntersuchungen für den Ausschluss bzw. die Bestätigung einer ALL unverzichtbar. In den vergangenen Jahrzehnten wurden erhebliche Fortschritte bei der Behandlung der ALL gemacht und sie gehört zu den wenigen disseminierten malignen Erkrankungen, die allein durch Chemotherapie geheilt werden können. Die Heilungsrate konnte von <10% vor 1980 auf nunmehr 30–40% verbessert werden. Der folgende Artikel bietet eine Übersicht über aktuelle diagnostische Verfahren, therapeutische Möglichkeiten, einschließlich der Stammzelltransplantation, über Prognosefaktoren und gibt einen Ausblick auf zukünftige Konzepte für Diagnostik und Therapie.

In patients with adult ALL, substantial progress has been made in the past 20 years. At present a cure rate of 30-40% can be achieved and varies in defined subgroups between 10-51%. ALL does not represent an uniform disease but is formed by biologic subentities, which differ in their natural history, clinical presentation and prognosis. A comprehensive diagnostic examination, including morphology, cytochemistry, immunology, cytogenetic and molecular genetic analysis is a precondition for prognostic assessment and therapeutic stratification. The basic principle of ALL treatment is a combination chemotherapy with sequential administration of induction, consolidation and maintenance therapy. Bone marrow transplantation has become an important part of the treatment strategy and is performed in patients with high risk. In the subgroup of T-ALL a significant progress has been made in the last years with survival rates of 40-50%. In B-ALL the results have been greatly improved to 48-51% by introduction of a specific treatment strategy. However, the results (about 30%) stagnate for the total group of B-lineage-ALL (common ALL, pre-B-ALL, pro-B-ALL). Patients with B-lineage-ALL can be subdivided in a high and low risk group according to the presence of risk factors (age, white blood cell count, time to achieve a complete remission, pro-B-ALL and the translocations t[4;11], t[9;22]). The outcome of the subgroup of adult pro-B-ALL has been substantially improved (50%). An increase of treatment results (20%) appears in outlines for patients above 50 years. The Ph/bcr-abl positive ALL has in spite of improved complete remission rates (60-70%) consistently unfavourable survival rates (10%).